Hepatitis B virus (HBV) infections are among the major global health problems. Particularly problematic is the high number of chronic courses of the disease, causing the deaths of more than 800,000 people globally every year. So far, there is no therapy to cure the condition. “With the discovery of a new hepatitis B virus in donkeys and zebras capable of causing prolonged infections, we now have the opportunity for a better understanding of the chronic course of the disease and thus also for mitigation or prevention of severe clinical consequences,” explains Prof. Dr. Jan Felix Drexler, DZIF researcher at the Charité — University Medicine Berlin. In the German Center for Infection Research (DZIF), he identifies and characterizes emerging viruses that could be dangerous for humans.
“Five years ago we were able to show for the first time that donkeys harbor viruses that are genetically related to the human hepatitis C virus,” explains Andrea Rasche, lead author of the study and DZIF scientist at the Charité — University Medicine Berlin. Since HBV and the hepatitis C virus (HCV) often occur together in humans, the researchers have also searched for HBV worldwide in donkeys. In addition to field work, extensive molecular, serological, histopathological and evolutionary biology methods were used. “We have studied nearly 3000 samples from equids, i.e. from donkeys, zebras and horses in five continents, and we found that donkeys are global carriers of the new hepatitis B virus,” explains Drexler.
The origins of the new HBV could be linked to the domestication of donkeys in Africa a few thousand years ago. Donkeys are naturally infected with HBV as well as with HCV. Zebras are also infected with HBV; horses are also likely to be receptive, but in initial studies, the scientists could not confirm any naturally infected horses. In naturally infected donkeys, the course of the infection is similar to chronic hepatitis B in humans.
“The new hepatitis B virus appears to use an unknown receptor for entry into the host cell,” explains Felix Lehmann, second lead author of the study and DZIF scientist at Giessen University (JLU) where he studied the molecular biology of virus binding and entry in cell culture. The emergence of human HBV and the development of its receptor use remain unclear and are jointly investigated by the researchers from Berlin and Giessen.
“Since the virus is unable to infect human liver cells, human infection with this virus can be ruled out with a high degree of probability,” emphasises Prof. Dr. Dieter Glebe, Head of the National Reference Centre for Hepatitis B and D viruses at JLU and DZIF scientist in the “hepatitis” research unit. The scientists are convinced that with the virus in donkeys and zebras, they can develop a better understanding of the pathogenesis of chronic hepatitis B and of HBV/HCV co-infection to lay a foundation for new therapies.
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A new study uncovers which cell types can be infected by SARS-CoV-2 due to their viral entry factors. The study also suggests that increased gene expression of these viral entry factors in some individuals partially explains the differences of COVID-19 severity reported in relation to age, gender and smoking status. The study evolved from the Human Cell Atlas Lung Biological Network with main contributions from Helmholtz Zentrum München, the Broad Institute of MIT and Harvard, the Wellcome Sanger Institute and University Medical Center Groningen.
COVID-19 does not affect everyone in the same way. While the coronavirus SARS-CoV-2 primarily manifests in the lung, it can infect other organs, too. Clinical observations throughout the pandemic also suggest that some population groups — such as elderly people, men and smokers — tend to be more severely affected by the disease. So far, the molecular reasons for this have not been described.
Previous studies had shown that in order to infect human cells, SARS-CoV-2 needs the cell to contain specific genetic viral entry factors — namely an ACE2 receptor and a protease (TMPRSS2 or CTSL). Knowing which cell types express both ACE2 and a protease would therefore give us information about which cells can potentially be infected with SARS-CoV-2.
The Human Cell Atlas (HCA) consortium is aiming to map every cell type in the human body, transforming our understanding of biology and disease. Within this, researchers from the HCA Lung Biological Network joined forces to contribute and analyse gene expression data from individual cells. Together, they analysed more than 100 datasets of single-cell gene expression of healthy people, to see which cell types express both ACE2 and a protease.
The analysis showed that specific cell types in the epithelium of the lung and airways, but also in the liver, the colon, and the eye are rich in genetic viral entry factors (=high expression of ACE2 receptor and a protease) — and therefore contain the necessary molecules to allow SARS-CoV-2 infection.
Moreover, the researchers found that the expression of genes underlying the viral entry factors is increased in the cells of elderly people and slightly in men compared to women. In addition, cells from smokers (in particular airway cells) express more SARS-CoV-2 entry factors than from non-smokers. These findings match differences in disease severity that have been reported for COVID-19 patients in those population groups and thus offer a molecular explanation for this difference (next to other factors which were not investigated in this study such as a weaker immune system).
Big data for biomedical research
“Fighting the pandemic, we cannot rely on conclusions that are limited to a few observations only. Instead, we must rely on robust analysis of big data. For example, to assess whether the ACE2 receptor required for virus entry is more abundant in cells of the elderly population, we need a strong representation of many diverse individuals in our dataset. Using data from the Human Cell Atlas, we could model how genetic viral entry factors in cells are expressed across the population,” says Malte Lücken, computational biologist at Helmholtz Zentrum München and co-first author of the study.
“A key aspect of this large-scale study was the age range of samples we were able to analyse. This study included data from human developmental stages, samples from children and young adults, as well as samples from elderly people. This gave us unique power to assess changes occurring over the human lifetime. The sheer scale of the data allowed us to see molecular differences with age, sex and smoking status,” said Kerstin Meyer, an author on the paper from the Wellcome Sanger Institute.
“This study was the epitome of a whole field coming together. Within the Human Cell Atlas consortium everyone who generated data on the healthy human lung contributed their data, both published and unpublished, to enable our analysis. When we then reached out beyond the consortium, more labs also contributed data to the effort. Only through these contributions was our analysis made possible,” adds Fabian Theis, Director of the Institute of Computational Biology at Helmholtz Zentrum München.
Strengths and limitations
The study investigated which cells are most likely to be infected by SARS-CoV-2. The results partially explain how disease severity might differ between population groups because of the molecular profile of cells. This provides a target for further intervention research. Moving forward, the findings may also help to better understand the spread of the corona virus across the body. The connection between viral entry factor expression and increased ease of infection or disease severity has been shown in mice and in the lab, but requires further validation in humans.

Researchers at Lund University in Sweden have designed a new bioink which allows small human-sized airways to be 3D-bioprinted with the help of patient cells for the first time. The 3D-printed constructs are biocompatible and support new blood vessel growth into the transplanted material. This is an important first step towards 3D-printing organs. The new study has been published in Advanced Materials.
Chronic lung diseases are the third leading cause of death worldwide with an EU cost of more than €380 billion annually. For many chronic diseases there is no cure and the only end-stage option for patients is lung transplantation. However, there are not enough donor lungs to meet clinical demand.
Therefore, researchers are looking at ways to increase the amount of lungs available for transplantation. One approach is fabricating lungs in the lab by combining cells with a bioengineered scaffold.
“We started small by fabricating small tubes, because this is a feature found in both airways and in the vasculature of the lung. By using our new bioink with stem cells isolated from patient airways, we were able to bioprint small airways which had multiple layers of cells and remained open over time,” explains Darcy Wagner, Associate Professor and senior author of the study.
The researchers first designed a new bioink (a printable material with cells) for 3D-bioprinting human tissue. The bioink was made by combining two materials: a material derived from seaweed, alginate, and extracellular matrix derived from lung tissue.
This new bioink supports the bioprinted material over several stages of its development towards tissue. They then used the bioink to 3D-bioprint small human airways containing two types of cells found in human airways. However, this bioink can be adapted for any tissue or organ type.
“These next generation bioinks also support the maturation of the airway stem cells into multiple cell types found in adult human airways, which means that less cell types need to be printed, simplifying the nozzle numbers needed to print tissue made of multiple cell types,” says Darcy Wagner.
Wagner notes that the resolution needs to be improved to 3D-bioprint more distal lung tissue and the air sacks, known as alveoli, that are vital for gas exchange.
“We hope that further technological improvements of available 3D printers and further bioink advances will allow for bioprinting at a higher resolution in order to engineer larger tissues which could be used for transplantation in the future. We still have a long way to go,” she says.
The team used a mouse model closely resembling the immunosuppression used in patients undergoing organ transplantation. When transplanted, they found that 3D-printed constructs made from the new bioink were well-tolerated and supported new blood vessels.
“The development of this new bioink is a significant step forward, but it is important to further validate the functionality of the small airways over time and to explore the feasibility of this approach in large animal models,” concludes Martina De Santis, the first author of the study.
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One of the most vital functions performed by the cells in our body is DNA repair, a task so crucial to our well-being that failing to execute it can lead to consequences as dreadful as cancer. The process of DNA repair involves a complex interplay between several gene pathways and proteins. One such pathway is the “Fanconi anemia (FA) pathway,” whose genes participate in DNA repair. FANCM, a component of this pathway, is tasked with the elimination of harmful DNA “inter-strand cross-links,” and interacts with another component called MHF in order to function. The importance of the FANCM-MHF complex is well-documented: its loss can result in chromosomal instabilities that can lead to diseases such as FA itself and cancer. However, little is known about its structure and the basis of its stability.
Against this backdrop, Associate Professor Tatsuya Nishino and his colleague Dr. Sho Ito from Tokyo University of Science decided to explore the crystalline structure of this intriguing complex using X-ray diffraction techniques. “DNA damage and chromosome segregation are mechanisms necessary for the maintenance and inheritance of genes possessed by all organisms. MHF (also known as CENP-SX) is an enigmatic complex that plays a role in DNA repair and chromosome segregation. We wanted to find out how it performs these two different functions in the hope that it might give us insights into novel phenomena,” explains Prof. Nishino. Their findings are published in Acta Crystallographica Section F: Structural Biology Communications.
The scientists prepared a recombinant version of the FANCM-MHF complex, consisting of FANCM from chickens and MHF1 and MHF2. They were able to purify three different types of protein crystals — tetrahedral, needle-shaped, and rod-shaped — from similar crystallization conditions. Surprisingly, upon determining the structure with X-ray crystallography, they found that two of the crystal forms (tetrahedral and needle-shaped) contained only the MHF complex without FANCM.
Intrigued by this discovery, the scientists used biochemical techniques to examine what caused the FANCM-MHF complex to disassemble. They attributed it to the presence of a compound called 2-methyl-2, 4-pentanediol (MPD), an organic solvent commonly used in crystallography, and exposure to an oxidizing environment.
But, how exactly does the dissociation happen? The scientists believe that this may have been caused partly by certain non-conserved amino acids in the chicken FANCM which causes the complex to aggregate with other FANCM-MHF complexes and disassemble. Additionally, they surmise that the small, flexible structure of MPD may have also allowed it to bind to and facilitate the release of FANCM, dismantling the complex.
The findings are extraordinary and can be used to improve the stability of the FANCM-MHF complex for future studies on its structure and function. Dr. Ito believes we have much to expect in the future from this complex. “A good understanding of this complex can help us treat cancer and genetic diseases, create artificial chromosomes, and even develop new biotechnological tools,” he speculates.
Thanks to Prof. Nishino and Dr. Ito’s efforts, we are already one step closer to that goal!
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An international team of scientists from the University of Turku, Finland and PennState University, USA have solved a long-standing mystery of how living organisms distinguish RNA and DNA building blocks during gene expression paving the way for the design of new antiviral drugs. The new insights were published in the journal Nature Communications.
All cellular organisms use two types of nucleic acids, RNA and DNA to store, propagate and utilize their genetic information. The synthesis of DNA is carried out by enzymes called DNA polymerases and is needed to accurately transfer the genetic information from generation to generation. Synthesis of RNA is carried out by enzymes called RNA polymerases and is needed to utilize the genetic information to ultimately produce proteins that in turn fulfil most structural and catalytic functions in all modern-day living organisms.
The ancient problem faced by RNA and DNA polymerases is that the DNA and RNA building blocks are very hard to distinguish. Those building blocks are identical except for a small part of the molecule, called the 2’OH group that is present in the RNA building blocks but is absent from the DNA building blocks.
DNA polymerases avoid using the RNA building blocks by featuring a cavity called the active site that is just big enough to bind the DNA building blocks but is too small to accommodate the slightly bigger RNA building blocks. As a result, only DNA building blocks bind to the active site cavity and get attached to the growing DNA polymer.
“RNA polymerases cannot use the same strategy because the smaller DNA building blocks will always fit into the same active site cavity as the RNA building blocks,” explains Senior Researcher Georgi Belogurov.
RNA Polymerase Active Site Cavity Deforms the DNA Building Blocks
To understand how RNA polymerases avoid using DNA building blocks, a research team from the University of Turku headed by Belogurov performed complex biochemical measurements using RNA polymerases that were altered by carefully engineered mutations. At the same time, the research team at Penn State University, USA, led by Professor Katsuhiko Murakami obtained a detailed three-dimensional structure of RNA polymerase with the DNA building block.

Our immune system is very successful when it comes to warding off viruses and bacteria. It also recognizes cancer cells as potential enemies and fights them. However, cancer cells have developed strategies to evade surveillance by the immune system and to prevent immune response.
In recent years, fighting cancer with the help of the immune system has entered into clinical practice and gained increasing importance as a therapeutical approach. Current therapies apply so-called immune checkpoint inhibitors. Immune checkpoints are located on the surface of cancer cells and slow down the immune response. Targeting these checkpoints can release this tumour-induced brake. Another strategy developed by cancer cells to escape the immune response is the production of the enzyme indoleamine-2,3-dioxygenase (IDO1), which metabolizes tryptophan into kynurenine and thereby interferes with the immune response in two ways: On the one hand, the depletion of tryptophan negatively impacts the growth of T cells, a central component of the immune response, which seek out and block cancer cells. On the other hand, the produced kynurenin inhibits T cells in the immediate environment of the cancer cells.
New Inhibitors against IDO1 — The Quest is on
IDO1 is in the focus of pharmaceutical research because of its cancer-driving effect. However, the search for IDO1 inhibitors has so far been only moderately successful and the first clinically tested IDO1 inhibitor, epacadostat, showed hardly any effect in clinical trials. However, it has not yet been possible to prove whether the inhibitor really blocks IDO1 in the tumour and whether the used dose is sufficient.
In drug discovery, experimental test procedures, so-called assays, are employed to search for new disease modulators in large libraries of thousands of compounds. For this purpose, mostly biochemical assays are applied, where a biochemical reaction is impaired if a substance shows an inhibitory effect in the assay. However, this method has certain disadvantages and limitations, as the test takes place in a test tube and not in the natural, cellular environment of the enzyme. For instance, enzymes like IDO1 are less stable and more reactive outside the protective shell of the cell. In addition, cell-free assays cannot detect indirect inhibitors of the enzyme, that for example interfere with its production or with essential co-factors.
Novel Cell-Based Assay Discovers IDO1 Inhibitors with Different Mechanisms of Action
Scientists led by Herbert Waldmann and Slava Ziegler have now developed a cell-based assay for the discovery of new IDO1 inhibitors that overcomes the limitations of cell-free assays. Elisabeth Hennes, PhD student at the MPI and first author of the study, employed a sensor that measures the conversion of the IOD1 substrate tryptophan into the metabolic product kynurenine in cell culture and thereby detects IDO1 activity. Based on this test strategy, several highly potent inhibitors with different mechanisms of action were identified from a library of more than 150,000 chemical substances: These include substances that directly switch off IDO1 as well as indirect inhibitors that prevent the production of IDO1 itself or that of its important cofactor heme.
“Unfortunately, previous attempts to find a compound that effectively stops the cancer-promoting activity of IDO1 in tumours have met with little success. However, the development of new compounds that can switch off IDO1 via different mechanisms of action could be a promising approach for immunotherapies in the fight against cancer. We hope that our newly developed cell-based assay could contribute to this area of research,” says Slava Ziegler.
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A team of scientists led by Dietmar Krautwurst from the Leibniz Institute for Food Systems Biology at the Technical University of Munich has now identified address codes in odorant receptor proteins for the first time. Similar to zip codes, the codes ensure that the sensor proteins are targeted from inside the cell to the cell surface, where they begin their work as odorant detectors. The new findings could contribute to the development of novel test systems with which the odorant profiles of foods can be analyzed in a high-throughput process and thus could be better controlled.
The genes of the approximately 400 human odorant receptor types have been identified for about 20 years. Nevertheless, for about 80 percent of these sensor proteins, it is still not known to which odorants they respond. Knowing this, however, is an important prerequisite for developing bio-based “artificial noses” for food controls.
Cellular test systems
But how can this problem be solved? Normally, scientists use cellular test systems to find out to which substances a receptor protein reacts. However, a particular problem with odorant receptors is that they often are stuck inside the test cells, and hardly reach the cell surface. Even for a suitable odorant it is then difficult to dock onto enough receptors to activate a cellular function. Thus, odorant assignment to individual receptor types is hampered.
However, why do odorant receptors so often become stuck in test cells, and what molecular mechanisms are involved in the transport of odorant receptors to the cell surface? To help answer these fundamental questions, the team of scientists examined and compared the protein sequences of 4,808 odorant receptors from eight different species using statistical and phylogenetic analysis methods. This enabled the team to identify highly conserved amino acid motifs. These are localized in the respective C-terminal end of the receptor proteins, which protrudes into the cell interior (cytoplasm).
Address codes identified
“The structure-function analyses we performed indicate that certain amino acid motifs and their combinations in different receptor types individually promote their cell surface expression and signaling. They function like address codes, or ‘zip codes’,” reports Dietmar Krautwurst, who led the study. “Such amino acid motifs were previously unknown for olfactory receptors,” the biologist continued. “We assume that the odorant receptor molecules interact with cellular proteins via these motifs, which guide the sensor proteins to their site of action on the cell surface via mechanisms that are still unknown.”

The snow may be melting, but it is leaving pollution behind in the form of micro- and nano-plastics according to a McGill study that was recently published in Environmental Pollution. The pollution is largely due to the relatively soluble plastics found in antifreeze products (polyethylene glycols) that can become airborne and picked up by the snow.
The researchers used a new technique that they have developed to analyze snow samples collected in April 2019 in Montreal for both micro- and nano-sized particles of various plastics. The McGill technique is orders of magnitude more sensitive than any of the other current methods used for tracing plastic in the environment. It allows scientists to detect ultra-trace quantities of many of the most common soluble and insoluble plastics in snow, water, rainfall, and even in soil samples once they have been separated — down to the level of a picogram (or one trillionth of a gram). It is based on using nano-structured mass spectrometry and, unlike other techniques currently in use, the new technique is both recyclable and based on sustainable practices.
“It is important to be able to detect even trace quantities of plastics in the environment,” says senior author, Parisa Ariya, from McGill’s Departments of Chemistry and Atmospheric and Oceanic Sciences. “Though these plastics may be harmless in themselves, they can pick up toxic organic matter and heavy metals from the environment, which can damage human cells and organs.”
The first author, Zi Wang, a PhD Candidate at McGill adds, “Our hope is that this new technique can be used by scientists in different domains gain key information about the quantity of micro- and nano-plastics in urban environments in order to better address their impacts on the ecosystem and on human health.”
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Many athletes, from football players to equestrians, rely on helmets to protect their heads from impacts or falls. However, a loose or improperly fitted helmet could leave them vulnerable to traumatic brain injuries (TBIs), a leading cause of death or disability in the U.S. Now, researchers reporting in ACS Sensors have developed a highly sensitive pressure sensor cap that, when worn under a helmet, could help reveal whether the headgear is a perfect fit.
According to the U.S. Centers for Disease Control and Prevention, 1.6 to 3.8 million sports- and recreation-related TBIs occur each year in the U.S. Field data suggest that loose or improperly fitted helmets can contribute to TBIs, but no devices currently exist that can provide information about how well a helmet conforms to an individual player’s head. To help observe and better understand helmet fit, Simin Masihi, Massood Atashbar and colleagues wanted to develop highly sensitive, fabric-based sensors that could map pressure in real-time.
The researchers made their sensors by placing a porous polydimethylsiloxane (PDMS) layer between two fabric-based, conductive electrodes. They created uniform pores in the PDMS layer by mixing and heating PDMS, sodium bicarbonate (also known as baking soda) and nitric acid, which released bubbles of carbon dioxide gas. When the team applied pressure to the sensor, the porous material compressed, causing a capacitance change as the space between the two electrodes decreased. To demonstrate a wearable helmet fit system, the researchers added 16 pressure sensors to different locations on a cap. Three volunteers wore the cap under a football helmet, and the sensors correctly revealed that the person with the largest head measurements felt the most pressure around his head, particularly in the front. The fit cap could help athletes select the proper off-the-shelf helmet for their head and allow manufacturers to develop custom helmets to reduce the severity of sports-related head injuries, the researchers say.
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Scientists at UC San Francisco have detected 109 chemicals in a study of pregnant women, including 55 chemicals never before reported in people and 42 “mystery chemicals,” whose sources and uses are unknown.
The chemicals most likely come from consumer products or other industrial sources. They were found both in the blood of pregnant women, as well as their newborn children, suggesting they are traveling through the mother’s placenta.
The study will be published March 17, 2021, in Environmental Science & Technology.
“These chemicals have probably been in people for quite some time, but our technology is now helping us to identify more of them,” said Tracey J. Woodruff, PhD, a professor of obstetrics, gynecology and reproductive sciences at UCSF.
A former EPA scientist, Woodruff directs the Program on Reproductive Health and the Environment (PRHE) and the Environmental Research and Translation for Health (EaRTH) Center, both at UCSF.
“It is alarming that we keep seeing certain chemicals travel from pregnant women to their children, which means these chemicals can be with us for generations,” she said.